Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats.
OBJECTIVE
We recently showed that activation of the hypothalamus-pituitary-adrenal axis may mitigate the progress of acute pancreatitis. To clarify the mechanism, the role of endogenous glucocorticoids in pancreatic acinar cell death was examined.


METHODS
The occurrence of apoptosis was studied in adrenalectomized or sham-operated rats with or without cerulein-induced pancreatitis. The effects of RU38486, a glucocorticoid-receptor antagonist, on the survival of cultured acinar cells (AR42J) were also examined.


RESULTS
Adrenalectomy caused increases in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) of acinar nuclei depending on the time after adrenalectomy but not of other cell types in the pancreas and in other digestive organs. Electron microscopy showed the characteristic features of apoptosis in the TUNEL-labeled acinar cells. In cerulein pancreatitis of adrenalectomized rats, the TUNEL-labeled acinar nuclei increased remarkably depending on the time after cerulein infusion. Replacement of glucocorticoids blocked the occurrence of apoptosis in these experiments. RU38486 induced dose dependently the apoptosis of AR42J cells.


CONCLUSIONS
These results provide evidence that endogenous glucocorticoids are an important factor for acinar cell survival. Endogenous glucocorticoids may protect acinar cells by decreasing their sensitivity to the induction of cell death during acute pancreatitis.
Kimura
K
K
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Shimosegawa
T
T
Sasano
H
H
Abe
R
R
Satoh
A
A
Masamune
A
A
Koizumi
M
M
Nagura
H
H
Toyota
T
T
D000208:Acute Disease; D000315:Adrenalectomy; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002108:Ceruletide; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000494:pharmacology; D005765:Gastrointestinal Agents; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D015735:Mifepristone / Q000494:pharmacology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors
D005765:Gastrointestinal Agents; D005938:Glucocorticoids; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D002108:Ceruletide